Premium
Structural insights into the regulation of human serine palmitoyltransferase complexes
Author(s) -
Lee ChiaHsueh,
Wang Yingdi,
Niu Yiming,
Zhang Zhe,
Gable Kenneth,
Gupta Sita,
Somashekarappa Niranjanakumari,
Han Gongshe,
Zhao Hongtu,
Myasnikov Alexander,
Kalathur Ravi,
Dunn Teresa
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2021.35.s1.04920
Subject(s) - sphingolipid , biogenesis , serine , substrate (aquarium) , chemistry , microbiology and biotechnology , biochemistry , enzyme , limiting , biology , ecology , gene , mechanical engineering , engineering
Sphingolipids are essential lipids in eukaryotic membranes. In humans, the first and rate‐limiting step of sphingolipid synthesis is catalyzed by the serine palmitoyltransferase (SPT) complex. The SPT complex consists of SPTLC1 and SPTLC2 as catalytic components, and ssSPTa and ORMDL3 as regulatory components. To understand the assembly, substrate processing and regulation of the complex, we determined cryo‐electron microscopy structures of the human SPT complex in various functional states at resolutions of 2.6–3.4 Å. The structures elucidate how catalytic components recognize the substrate, as well as how regulatory components modulate the substrate‐binding tunnel to control enzyme activity. These findings reveal the molecular mechanism of sphingolipid biogenesis governed by the serine palmitoyltransferase complex.